tbuckley/cabot-search huggingface dataset:
AB0844 Characterizing Gut Microbial Enterotypes in undifferentiated spondyloarthritis
Authors: Y. Zhang, S. X. Zhang, J. Qiao, S. Song, R. Zhao, X. Li
Journal: Annals of the Rheumatic Diseases (2022)

Background The presence of dysbiosis in the gut microbiome is responsible for the initiation of autoinflammatory and autoimmune diseases. However, such dysbiosis is difficult to characterize in sweeping generalization owing to the high dimensional complexity of the gut microbiota. Objectives This study designed to characterize the gut microbial enterotype in patients with undifferentiated spondyloarthritis (USpA) from lower dimensionality and describe the dysbiosis. Methods The Fecal samples of 105 patients were diagnosed with USpA and gender- and age- matched 105 healthy controls (HC) were included in the intestinal microbiota composition analyses via Illumina sequencing of bacterial 16S rRNA genes. Microbiota-derived clustering was performed using Dirichlet multinomial mixtures (DMM) modeling. To identify discriminative features in abundance between enterotypes, the Linear Discriminant Analysis Effect Size (LEfSe) algorithm was used with the online interface Galaxy (Log10 LDA score &gt; 4.0). The phyloseq R package to compute alpha diversity (ACE, Chao1, Shannon and Simpson indices), beta diversity (Bray-Curtis dissimilarity) and the microbial composition (at the genus level) to describe the richness and diversity of the microbiota between two enterotypes. Results As showed in Figure 1A and C, by evaluating the Laplace approximation to the negative log mode, 2 distinctly enterotypes were identified in the USpA and HC microbiota dataset. LEfSe Analysis indicated the distinctive abundant microbial clades between the 2 enterotypes (LDA score &gt;4) in both the USpA and HC group respectively. At the genus level, Faecalibacterium and Prevotella was the driving genus of enterotype 1 and Bacteroides contributed to enterotype 2 (Figure 1B, D). The alpha-diversity and beta diversity between the distinctive enterotypes was highly significantly different (P &lt; 0.01, Figure 1E, F). Distinct bacterial profiles were also observed in enterotype 1 and 2 (Figure 1G). Interestingly, no significant differences were found between USpA patients and HC for the corresponding same intestinal type. This may be because USpA was at a comparatively early stage of spondyloarthritis (SpA). Conclusion Two significantly distinct bacterial microbiota structures existed in the USpA patients which was consistent with the general healthy population. References [1]Belkaid Y, Hand TW: Role of the microbiota in immunity and inflammation . Cell 2014, 157 (1):121-141. Acknowledgements This work was supported by the National Natural Science Foundation of China (No. 82001740). Disclosure of Interests None declared
POS0996 EFFECTS OF DISEASE MODIFYING ANTI RHEUMATIC DRUGS ON SACROILIAC MRI SCORE IN AXIAL SPONDYLOARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.
Authors: A. Hansmaennel, A. Gerazime, O. Fakih, M. Chouk, C. Prati, D. Wendling, F. Verhoeven
Journal: Annals of the Rheumatic Diseases (2022)

Background Sacroiliac bone marrow edema is an important factor in the diagnosis and management of axial spondyloarthritis (axSpA). Objectives The aim of this meta-analysis is to assess the effect of the different bDMARDs and tsDMARDs on the SPARCC score at 12-16 and 48-52 weeks. Methods A systematic review, performed on Pubmed, Embase and Cochrane databases, included randomized controlled studies evaluating the sacroiliac joint (SIJ) SPARCC score at 12-16 or 48-52 weeks in patients with axSpA meeting the ASAS 2009 criteria or the modified New York criteria. We included studies evaluating the effects of the different treatments on the SPARCC score of SIJ in axial spondyloarthritis in comparison to a control group. Results Fifteen studies were included in the meta-analysis. Nine studies evaluated the effect of TNF inhibitors (TNFi), two for ixekizumab, one for filgotinib and one for tofacitinib. At 12 and 16 weeks, SIJ SPARCC score was significantly improved by TNFi (WMD: - 3.29 [95% CI -4.25; -2, 34]), IL-17 inhibitors (WMD: - 3.98 [95% CI –5.76; -2.20]) and by JAK inhibitors (JAKi) (WMD: - 3.02 [95% CI -4.54; -1.51]). There was no difference between the molecule subgroups. At 48-52 weeks, TNFα inhibitors, introduced at baseline, reduced more SIJ SPARCC, but not significantly (WMD: -2.26 [95% CI -4.94; 0.42]), than placebo groups who began a TNFi treatment with delay. Conclusion Our meta-analysis shows a comparable improvement of the SIJ SPARCC score regarding TNFi, JAKi and IL-17 inhibitors at three months and suggests the presence of an opportunity window. Figure 1. Forest plot of SPARCC SIJ score for all therapeutic agents versus controls at week 12-16. Disclosure of Interests None declared
Clinically unquestionable but histologically deceptive melanomas in acral skin grafts: PRAME confirms its role
Authors: Giacomo Santandrea, Riccardo Valli, Moira Ragazzi, Fabio Castagnetti, Michela Lai, Caterina Longo, Simonetta Piana
Journal: British Journal of Dermatology (2022)

The aim of this study was to investigate the role of PRAME in reducing the risk of an underestimation of tumour margins, in a consecutive series of acral melanomas recurring on skin grafts.
AB1245 HOSPITAL ADMISSION RATES FOR JUVENILE IDIOPATHIC ARTHRITIS IN WESTERN AUSTRALIA HAVE NOT CHANGED FOLLOWING THE INTRODUCTION OF BIOLOGICAL DRUG THERAPY.
Authors: E. Kelty, E. Quintrell, P. Manners, D. Preen, J. Nossent
Journal: Annals of the Rheumatic Diseases (2022)

Background Aggressive treatment with disease modifying drugs to reach early disease remission has become standard of care for juvenile idiopathic arthritis (JIA) in Australia this millennium (1,2). Objectives We examined whether this modern approach including the availability of subsidised TNF inhibitor treatment has led to a change in the rate of first hospitalisation for JIA patients in Western Australia (WA). Hospital data were also used to estimate a minimum prevalence of JIA in WA. Methods State-wide hospital data were used to identify patients aged 15 years and younger with a first hospitalisation for JIA between 1990 and 2012. Changes in the hospitalisation rate over time were examined using join-point regression. State-wide PBS prescription data on TNFi (available for JIA since 2004) were obtained from Services Australia and expressed as defined daily dose /1000/day (DDD). Results We identified 786 unique cases of JIA in WA hospital records. At the time of the index hospitalisation, patients were on average 7.6 (± 4.4) years of age and female patients made up the majority of cases (n=465, 59.2%). The overall rate for a first hospitalization for JIA was 7.9 (95%CI: 7.3, 8.4) per 100,000 children ≤15 years, and did not change significantly over the study period (annual percentage change (APC): 1.3, 95%CI -0.3, 2.8), although TNFi usage increased linearly and DDD reached 0.3 at the end of study. The hospital-based prevalence of JIA in 2012 reached 114.5/100.000 for girls (0.12%) and 52.9/100.000 for boys (0.05%). Conclusion The hospital based (i.e. minimum) prevalence of JIA in WA aligns with international data. Rates for a first hospitalization for JIA have not decreased during a time when early aggressive therapy became common practice and TNFi use for JIA reached 30/100.000. This unexpected finding requires further investigation. References [1]Georgina Tiller, Joanne Buckle, Roger Allen et al. Juvenile idiopathic arthritis managed in the new millennium: one year outcomes of an inception cohort of Australian children. Pediatric Rheumatology (2018) 16:69 [2]Jane Munro, Emily Haesler, Jiri Rada,Amy Jasper. Juvenile idiopathic arthritis: a literature review of recent evidence. The Royal Australian College of General Practitioners, August 2009 Acknowledgements Supported by a grant from The Arthritis Foundation of Western Australia Disclosure of Interests None declared
POS1168 TREAT TO TARGET OF GOUT: AN EVIDENCE-BASED CONSENSUS ON CLINICAL PRACTICE GUIDELINES
Authors: Y. El Miedany, M. H. Abu-Zaid, M. Elgaafary, N. Ali, M. Mansour, W. Hassan, M. A. Mortada, M. Eissa, S. A. A. Tabra, N. Fouad, R. Ali, B. M Medhat, Y. Adel Abdelsalam Hussein, R. M. Ghaleb, E. Nourhan Elameen, S. Saber, S. Moussa
Journal: Annals of the Rheumatic Diseases (2022)

Background New therapies, management approaches and evidence regarding the management of gout have become available over the past years. This triggered the need for updated recommendations for the management of gout. Objectives to develop an up-to-date consensus evidence-based clinical practice guideline for the management of gout including recommendations for management of acute gout flares, optimum usage of urate lowering therapy for chronic gout as well as patient education and lifestyle guidance. Methods An extensive systematic literature review was performed, and evidence-based recommendations were extrapolated, based on 16-key questions identified according to population, intervention, comparator, and outcomes (PICO) approach. For each item, the level of evidence was determined using the Oxford Centre for Evidence-based Medicine (CEBM) system. These were evaluated by a panel of 17-experts via online surveys over a 2-round Delphi process. Results At the end of round 2, a total of 30-recommendation items, categorized into 10 domains to were obtained. Agreement with the recommendations (rank 7-9) ranged from 90-100%. Consensus was reached (i.e.≥75%of respondents strongly agreed or agreed) on the wording, the grade of recommendation and level of evidence of all the 30 clinical standards identified by the scientific committee. The guideline emphasized that all gouty patients should be screened for comorbidities. Based on this, an algorithm for treat to target management approach tailored to the individual patient’s needs and associated comorbidities has been outlined. Conclusion This work provides updated evidence-based recommendations for the prevention and treatment of acute as well as chronic gouty arthritis. It provides an approach for physicians and patients making decisions on the management of gout. It will also facilitate improvement and uniformity of care. Disclosure of Interests None declared
AB0700 HIGH BRONCHOALVEOLAR FLUID NEUTROPHILS INDEPENDENTLY PREDICT 15-YEAR MORTALITY IN SCLERODERMA PATIENTS WITH INTERSTITIAL LUNG DISEASE NAIVE TO IMMUNOSUPPRESSANTS
Authors: E. De Lorenzis, G. Natalello, L. Verardi, P. G. Cerasuolo, G. Alonzi, M. A. D’Agostino, S. L. Bosello
Journal: Annals of the Rheumatic Diseases (2022)

Background Scleroderma interstitial lung disease (SSc-ILD) has a variable and poorly predictable course. Data about the role of bronchoalveolar lavage fluid (BALF) analysis in prognostic stratification of SSc-ILD patients (pts) are conflicting. Objectives To assess BALF analysis role in prognostic stratification of SSc-ILD pts. Methods Forty SSc-ILD pts naive to immunosuppressants underwent comprehensive clinical evaluation, BALF analysis with total and differential leukocyte count, pulmonary function tests (PFTs), high-resolution computed tomography (HRCT) of the chest. All pts had fibrosing lung disease affecting more than 10% of lung volume on HRCT. Baseline alveolar and interstitial scores were computed. The 15-year crude mortality rate was retrospectively assessed. Results The enrolled pts (male 20%, aged 53.9±13 years) had a disease duration of4.3±3.4 years. Diffuse cutaneous involvement LeRoy variant was present in 47.5% of pts, while anti-Scl70 and anti-centromere antibodies were detected in 57.5% and 12.5% of pts, respectively. The average alveolar and interstitial scores were 6.5±4.8 and 6.2±2.7, respectively; 25% of the pts had FVC less than or equal to 80% and 35% had DLco less than or equal to 80%. During the follow-up, 18 pts (45%) received immunosuppressants. BALF neutrophilia (&gt; 3%), eosinophilia (&gt;1%) and lymphocytosis (&gt;15%) were reported in 40%, 16% and 5% of pts, respectively. Twenty-five pts (62.5%) died within 15 years after bronchoscopy. Fifteen-year mortality was predicted by neutrophilia (HR 5.5, 95% IC 1.9-15.7), log-transformed total cell count (HR 2.5, 95% IC 1.1-5.7), absolute neutrophil (HR 1.8, 95% IC 1.3-2.5) and eosinophil (HR 1.3, 95% IC 1.1-1-6) cell counts, and macrophage (HR 0.1, 95% IC 0-0.6), neutrophil (HR 1.9, 95% IC 1.3-2.7), and eosinophil (HR1.3, 95% IC 1-1.7) percentages. Only absolute and relative neutrophil counts were independently associated with mortality also in regression models adjusted for demographics (age, gender), main disease traits (diffuse cutaneous variant, anti-Scl70 positivity), pulmonary function tests (FVC, DLco), HRCT involvement (alveolar and interstitial scores) and vascular complications (presence of pulmonary hypertension, digital ulcers). Conclusion High BALF neutrophils were associated with high 15-year mortality independently from established clinical risk factors. BALF analysis could improve prognosis prediction in SSc-ILD pts. Disclosure of Interests None declared
AB0672 Functional capacity and quality of life in patients with systemic sclerosis – data from Moscow register of patients with systemic sclerosis
Authors: A. Klimenko, E. Zhilyaev, E. Mikheeva, N. Shostak, N. Babadaeva, A. Kondrashov, N. Demidova, D. Khorolskii
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic sclerosis (SSc) is a multisystem, connective tissue disease characterized by fibrosis of the skin and internal organ involvement, which can influence quality of life and functional capacity. SSc patients show some problems associated with reduced quality of life. Objectives Systemic sclerosis (SSc) is a multisystem, connective tissue disease characterized by fibrosis of the skin and internal organ involvement, which can influence quality of life and functional capacity. SSc patients show some problems associated with reduced quality of life. Methods In total, 51 patients with SSc were included: 50 women and 1 man (mean age: 63,2 ± 10,1 year, limited SSc 28/diffuse SSc 23, median duration since first non-Raynaud symptom: 10,1 years) who fulfilled the ACR/EULAR classification criteria (2013), filled in questionnaires assessing disability (HAQ, Health Assessment Questionnaire) and quality of life (SF-36, Medical outcomes study Short Form 36 - Physical Component Summary and Mental Component Summary). Results Average HAQ in patients with limited and diffuse SSc was 0,66±0,58 and 0,9±0,59. Data analysis showed that 59% of the patients were in the mild to moderate HAQ disability category (0 ⩽ HAQ &lt; 1), 39% in the moderate to severe disability category (1 ⩽ HAQ &lt; 2), and 2% in the severe to very severe disability category (2 ⩽ HAQ ⩾ 3). The SF36 mean scores of the total group were 34,8±8,7 on the Mental Component Summary and 37,0±13,1 on the Physical Component Summary. Conclusion Ssc and its complications decrease quality of life and functional capacity. Although validated in SSc, the HAQ disability index underestimates respiratory failure due to interstitial lung disease, gastrointestinal symptoms, cardiovascular complications and severity of Raynaud phenomenon. Alternative measures of functional impairment should be examined. Health-related quality of life, which was assessed by the SF-36 is reduced in both physical and mental domains. It should be taken into account by clinicians for further improvement of treatment and development rehabilitation program. References [1]Almeida C, Almeida I, Vasconcelos C. Quality of life in systemic sclerosis. Autoimmun Rev . 2015;14(12):1087-1096 Disclosure of Interests None declared
POS0634 SAFETY PROFILE OF b/tsDMARD IN RHEUMATOID ARTHRITIS PATIENTS WITH IMPAIRED GLOMERULAR FILTRATION RATE. AN ANALYSIS FROM THE GISEA REGISTRY.
Authors: M. Fornaro, F. Franceschini, E. Gremese, A. Cauli, M. Sebastiani, C. Montecucco, F. Conti, M. Rossini, R. Foti, F. P. Cantatore, E. Fusaro, C. Lomater, B. Frediani, M. Govoni, F. Atzeni, R. Ramonda, S. D’angelo, G. Ferraccioli, G. Lapadula, R. Caporali, F. Iannone
Journal: Annals of the Rheumatic Diseases (2022)

Background In real-life setting, a greater number of elderly rheumatoid arthritis (RA) patients with impaired glomerular filtration rate (GFR) needs treatment with biologic or target synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) to achieve disease control and reduce NSAIDs intake. Long-term observational data from the real-life on the use of b/tsDMARD in these patients are scarce. Objectives The aim of this study was to evaluate the retention rate of b/tsDMARD in RA patients with impaired GFR in real-life setting. Methods Data of RA patients treated with at least one b/tsDMARD were retrospectively analyzed form the national Italian GISEA registry from January 2016 to December 2021. Estimated-GFR (eGFR) was calculated with the Cockcroft-Gault equation at the time of any b/tsDMARD prescription. For the purpose of this study, patients were divided in two groups, patients with impaired GFR (eGFR ≤60) and patients with normal GFR (eGFR &gt;60). The retention rate was calculated by the Kaplan-Meier method and compared between these two groups by a log-rank test. Results The study population included 2443 treatment-line with b/tsDMARD from 1888 patients (female 80.4%, age 57±12 years, mean baseline CDAI 17±12, FR/ACPA+ 69.5%) who started a new b/tsDMARD. Disease characteristics are shown in Table 1. 288 treatments with b/tsDMARD were started in patients with impaired eGFR and 2155 in patients with normal eGFR. Compared to patients with eGFR &gt;60, patients with eGFR ≤60 showed higher HAQ-DI (1.3±0.8 vs 1±0.8, p&lt;0.001) at the start of b/tsDMARD treatment. Glucocorticoids were more prescribed in patients with impaired eGFR (80.2% vs 72.8%, p&lt;0.01), while csDMARDs were more prescribed in association with b/tsDMARD in patients with normal eGFR (83.1% vs 76.4%, p&lt;0.01). Of note, CTLA4-Ig treatment was more prescribed in patients with impaired eGFR (26% vs 17.1%, p&lt;0.05), while no difference in b/tsDMARD prescription was observed for other mechanism of actions. Drug survival was similar between RA patients with impaired eGFR [58.2%, mean survival time 35 months (CI95% 31-39)]and RA patients with normal eGFR [55%, mean survival time 34.4 months (CI95% 33-36), log rank: 0.88] (Figure 1). Cox regression model adjusted for age, sex and b/tsDMARD showed no impact of eGFR on drug survival [HR: 0.9 (CI95%: 0.7-1.2). Conclusion Our data show that impaired eGFR seems to not influence the persistence of b/tsDMARD treatment in RA patients. Disclosure of Interests None declared
AB0076 DOES HELICOBACTER PYLORI HAVE AN IMPACT ON RHEUMATOID ARTHRITIS?
Authors: H. Wu, C. Wu
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is an autoimmune disease of not completely defined pathogenesis. A growing body of studies shows that microbiota may be a critical environmental trigger in the development of RA. Helicobacter pylori (Hp) is a common human pathogenic bacterium and is associated with multiple autoimmune diseases. However, the role of H.pylori in RA is far less well understood. Objectives The study aims to investigate the impact of Hp on RA. Methods We recruited 81 RA patients (disease duration &gt;1 year) in this study, and all patients met the 2010 ACR/EULAR diagnostic criteria. They were divided into two groups depending on their infection status: the Hp-uninfected group (9 male, 33 female) and the Hp-infected group (10 male, 29 female). C-reactive protein (CRP), Rheumatoid factor (RF), and Anti-citrullinated protein antibodies (ACPA) were measured in serum of patients for assessing disease severity. Results The results, as shown in Figure 1, indicated that the serological levels of CRP (P=0.004), RF (P=0.0004), and ACPA (P=0.009) were significantly elevated in the Hp-positive group compared to the Hp-negative group. Figure 1. The serological levels of CRP (A), RF (B), and ACPA (C) in two groups. *P&lt;0.05, **P&lt;0.01, ***P&lt;0.001. Conclusion Hp-positive RA patients present with higher levels serological of CRP, RF, and ACPA, which suggested that Hp infection could influence the disease progression or severity of RA. Thus, further research is required to investigate the pathogenic mechanism of Helicobacter pylori in rheumatic diseases. Disclosure of Interests None declared
Impairment of the NKT–STAT1–CXCL9 Axis Contributes to Vessel Fibrosis in Pulmonary Hypertension Caused by Lung Fibrosis
Authors: Katharina Jandl, Leigh M. Marsh, Ayse Ceren Mutgan, Slaven Crnkovic, Francesco Valzano, Diana Zabini, Julia Hoffmann, Vasile Foris, Elisabeth Gschwandtner, Walter Klepetko, Helmut Prosch, Holger Flick, Luka Brcic, Izidor Kern, Akos Heinemann, Horst Olschewski, Gabor Kovacs, Grazyna Kwapiszewska
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Pulmonary hypertension (PH) is a common, severe comorbidity in interstitial lung diseases such as pulmonary fibrosis (PF), and it has limited treatment options. Excessive vascular fibrosis and inflammation are often present in PH, but the underlying mechanisms are still not well understood. Objectives: To identify a novel functional link between natural killer T (NKT) cell activation and vascular fibrosis in PF-PH. Methods: Multicolor flow cytometry, secretome, and immunohistological analyses were complemented by pharmacological NKT cell activation in vivo, in vitro, and ex vivo. Measurements and Main Results: In pulmonary vessels of patients with PF-PH, increased collagen deposition was linked to a local NKT cell deficiency and decreased IL-15 concentrations. In a mouse model of PH caused by lung fibrosis, pharmacological NKT cell activation using a synthetic α-galactosylceramide analog (KRN7000) restored local NKT cell numbers and ameliorated vascular remodeling and right ventricular systolic pressure. Supplementation with activated NKT cells reduced collagen deposition in isolated human pulmonary arterial smooth muscle cells (hPASMCs) and in ex vivo precision-cut lung slices of patients with end-stage PF-PH. Coculture with activated NKT cells induced STAT1 signaling in hPASMCs. Secretome analysis of peripheral blood mononuclear cells identified CXCL9 and CXCL10 as indicators of NKT cell activation. Pharmacologically, CXCL9, but not CXCL10, potently inhibited collagen deposition in hPASMCs via the chemokine receptor CXCR3. Conclusions: Our results indicate that the absence of NKT cells impairs the STAT1-CXCL9-CXCR3 axis in PF-PH and that restoration of this axis by NKT cell activation may unravel a novel therapeutic strategy to target vascular fibrosis in interstitial lung disease.